Gene therapy approach has been adopted to treat HIV infection. A potentially attractive class of anti-HIV-1 genes is ribozymes, which have been targeted to specific sites of HIV-1-RNA. Ribozymes are RNA sequences, which have an ability not only to bind to but also to cleave RNA. The City of Hope has been involved in a clinical trial in which a tandem pair of anti-tat and anti-tat/rev ribozymes have been transduced into autologous CD34+ cells by a vector derived from Moloney murine leukemia virus (MoMLV) and reinfused into the patients. In contrast to vectors derived from MLA, lentiviral vectors derived from human immunodeficiency virus (HV) or feline could be due to the ability of lentiviruses to infect quiescent or terminal differentiated cells whereas MLV fails to infect. In our preliminary studies, we have produced high- titer HIV and FIV vectors from transfected 293T cells. We have shown that these two vectors are able to transduce cultured quiescent fibroblasts and slow growing cells much more efficiently than a MLV vector. We now propose to use lentiviral vectors to deliver anti-HIV ribozyme genes into human CD34+ cells. We will (1) compare the transduction efficiency of human CD34+ cells with the HIV, FIV and MLV vectors; (2) compare different promoters in lentiviral vectors for efficient gene expression in CD34+ cells; (3) test the efficacy of ribozymes delivered by the lentiviral vectors; (4) establish stable human packaging cell lines for lentiviral vectors.